Correcting segmentation of medical images using a statistical analysis of historic corrections

ABSTRACT

Disclosed is a computer-implemented methods of determining distributions of corrections for correcting the segmentation of medical image data, determining corrections for correcting the segmentation of medical image data, training a learning algorithm for determining a segmentation of a digital medical image, and determining a relation between an image representation of the anatomical body part in an individual medical image and a label to be associated with the image representation of the anatomical body part in the individual medical image using the trained machine learning algorithm. The methods encompass reading a plurality of corrections to image segmentations, wherein the corrections themselves may have been manually generated, transforming these corrections into a reference system which is not patient-specific such as an atlas reference system, conducting a statistical analysis of the correction, and applying the re-transformed result of the statistical analysis to patient images. The result of the statistical analysis may also be used to appropriately train a machine learning algorithm for automatic segmentation of patient images. The application of such a trained machine learning algorithm is also part of this disclosure.

FIELD OF THE INVENTION

The present invention relates to a computer-implemented method of determining distributions of corrections for correcting the segmentation of medical image data, methods for correcting the segmentation using the determined distributions of corrections, a corresponding computer program, a computer-readable storage medium storing such a program and a computer executing the program, as well as a medical system comprising an electronic data storage device and the aforementioned computer.

TECHNICAL BACKGROUND

It is known to manually generate a correction of image segmentation and to positionally transform the correction into a coordinate space which is not patient-specific, e.g. for reasons of data security. However, this correction by itself provides no reliable measure for quantifying the reliability of the applied segmentation algorithm and does not provide for any consideration of regions of low reliability of the segmentation algorithm during the correction process.

The present invention has the object of providing an improved method of correcting image segmentations.

Aspects of the present invention, examples and exemplary steps and their embodiments are disclosed in the following. Different exemplary features of the invention can be combined in accordance with the invention wherever technically expedient and feasible.

EXEMPLARY SHORT DESCRIPTION OF THE INVENTION

In the following, a short description of the specific features of the present invention is given which shall not be understood to limit the invention only to the features or a combination of the features described in this section.

The disclosed method encompasses reading a plurality of corrections to image segmentations, wherein the corrections themselves may have been manually generated, transforming these corrections into a reference system which is not patient-specific such as an atlas reference system, conducting a statistical analysis of the correction, and applying the re-transformed result of the statistical analysis to patient images. The result of the statistical analysis may also be used to appropriately train a machine learning algorithm for automatic segmentation of patient images. The application of such a trained machine learning algorithm is also part of this disclosure.

GENERAL DESCRIPTION OF THE INVENTION

In this section, a description of the general features of the present invention is given for example by referring to possible embodiments of the invention.

In general, the invention reaches the aforementioned object by providing, in a first aspect, a computer-implemented method (for example, medical method) of determining distributions of corrections for correcting the segmentation of medical image data. The method according to the first aspect comprises executing, on at least one processor of at least one computer (for example at least one computer being part of a navigation system), the following exemplary steps which are executed by the at least one processor.

In a (for example first) exemplary step of the method according to the first aspect, initial segmented patient image data is acquired which describes an initial segmentation of digital medical images of an anatomical body part of a first plurality of patients. The digital medical images are for example two-dimensional images (such as radiographies) or three-dimensional images (i.e. tomographies such as computed x-ray tomographies or magnetic resonance tomographies or sonographies) In a (for example second) exemplary step of the method according to the first aspect, segmentation correction data is acquired which describes a correction of the initial segmentation for each patient of the first plurality of patients. For example, the segmentation correction data is acquired based on user input, for example it has been generated by manually creating the correction.

In a (for example third) exemplary step of the method according to the first aspect, atlas data is acquired which describes an image-based model of the anatomical body part.

In a (for example fourth) exemplary step of the method according to the first aspect, correction transformation data is determined based on the segmentation correction data and the atlas data, wherein the correction transformation data describes a transformation (for example, a mapping) for transforming the corrections into a reference system used for describing positions in the image-based model.

In a (for example fifth) exemplary step of the method according to the first aspect, transformed correction data is determined based on the segmentation correction data and the correction transformation data by applying the transformation to the corrections to determine transformed corrections.

In a (for example sixth) exemplary step of the method according to the first aspect, combined correction data is determined based on the transformed correction data, wherein the combined correction data describes the results of a statistical analysis of the corrections. For example, the result of the statistical analysis constitutes a statistical distribution of the corrections for the first plurality of patients. For example, the statistical analysis is an averaging analysis.

In a second aspect, the invention is directed to a computer-implemented method (for example, medical method) of determining corrections for correcting the segmentation of medical image data. The method according to the second aspect comprises executing, on at least one processor of at least one computer (for example at least one computer being part of a navigation system), the method according to the first aspect and the following exemplary steps which are executed by the at least one processor.

In a (for example first) exemplary step of the method according to the second aspect, segmented individual patient image data is acquired which describes a segmentation of an anatomical body part of a patient in a digital individual medical image. The individual patient image has been generated for example with the same imaging modality as the digital medical images from which the initial segmentation has been generated.

In a (for example second) exemplary step of the method according to the second aspect, correction re-transformation data is determined based on the atlas data and the segmented individual patient image data. The correction re-transformation data describes a transformation (for example, a mapping) for transforming the results of the statistical analysis of the corrections into a reference system used for describing positions in the digital individual medical image.

In a (for example third) exemplary step of the method according to the second aspect, re-transformed correction data is determined based on the combined correction data and the correction re-transformation data.

In a (for example fourth) exemplary step of the method according to the second aspect, corrected segmented patient image data is determined based on the segmented individual patient image data and the re-transformed correction data, wherein the corrected segmented patient image data describes a result of applying the corrections to the segmentation of the anatomical body part of the patient in the digital individual medical image. For example, the result of applying the corrections to the segmentation of the anatomical body part of the patient in the digital individual medical image is determined by applying the corrections in dependence on a characteristic quantity of the result of the statistical analysis. For example, the characteristic quantity is an average, for example an arithmetic average, or a variance.

In a third aspect, the invention is directed to a computer-implemented method (for example, medical method) of training a learning algorithm for determining a segmentation of a digital medical image. The method according to the third aspect comprises executing, on at least one processor of at least one computer (for example at least one computer being part of a navigation system), the method according to the first or second aspect and the following exemplary steps which are executed by the at least one processor.

In a (for example first) exemplary step of the method according to the third aspect, training patient image data is acquired which describes digital medical images of an anatomical structure of a second plurality of patients.

In a (for example second) exemplary step of the method according to the third aspect, label data is acquired which describes positions of labels assigned to the training patient image data, wherein the positions of the labels are defined in the reference system in which positions in the training patient image data are defined.

In a (for example third) exemplary step of the method according to the third aspect, transformed statistical distribution data is determined based on the training patient image data and the combined correction data, wherein the transformed statistical distribution data describes the result of transforming the statistical distributions into the reference system in which positions in the training patient image data are defined.

In a (for example fourth) exemplary step of the method according to the third aspect, statistics assignment data is determined based on the transformed statistical distribution data and the label data, wherein the statistics assignment data describes an assignment of the results of the statistical analysis to the labels.

In a (for example fifth) exemplary step of the method according to the second aspect, label relation data is determined which describes model parameters (for example, weights) of a learning algorithm for establishing a relation between the position of an anatomical structure in each medical image of the second plurality of patients and the position of its associated label, wherein the label relation data is determined by inputting the training patient image data and the label data and the transformed statistical distribution data into a function which establishes the relation. For example, the combined correction data serve as a basis for determining weights which are input e.g. into a cost or loss function that compares the established relation to the label data.

This allows judging the quality of the training result while putting an emphasis on regions in the segmentations of the medical images which were subject to strong corrections.

In an example of the method according to the third aspect, the relation between the position of an anatomical structure in each medical image of the second plurality of patients and the position of its associated label is defined as a relative position between the position of an anatomical structure in each medical image of the second plurality of patients and the position of its associated label, and the learning algorithm determines the relative position based on the transformed statistical distribution data.

In an example of the method according to the third aspect, the learning algorithm comprises or consists of a machine learning algorithm.

In an example of the method according to the third aspect, the learning algorithm comprises or consists of a convolutional neural network.

In an example of the method according to the third aspect, the model parameters define the learnable parameters, for example weights, of the learning algorithm.

In a fourth aspect, the invention is directed to a computer-implemented method (for example, medical method) of determining a relation between an image representation of the anatomical body part in an individual medical image and a label to be associated with the image representation of the anatomical body part in the individual medical image. The method according to the fourth aspect comprises executing, on at least one processor of at least one computer (for example at least one computer being part of a navigation system), the following exemplary steps which are executed by the at least one processor.

In a (for example first) exemplary step of the method according to the fourth aspect, individual patient image data is acquired which describes a digital individual medical image describing an anatomical body part of a patient. The individual patient image has been generated for example with the same imaging modality as the digital medical images from which the initial segmentation has been generated.

In a (for example second) exemplary step of the method according to the fourth aspect, segmented individual patient image data is determined which describes a relation between the image representation of the anatomical body part in the individual medical image and a label to be associated with the image representation of the anatomical body part in the individual medical image. The segmented individual patient image data is determined by inputting the individual patient image data into a function which establishes the relation between the image representation of the anatomical body part in the individual medical image and a label to be associated with the image representation of the anatomical body part in the individual medical image. The function is part of a learning algorithm which has been trained by executing the method according to the third aspect.

In an example of the method according to the fourth aspect, the learning algorithm has been trained by executing the method according to the third aspect, wherein the relation between the position of an anatomical structure in each medical image of the second plurality of patients and the position of its associated label is defined as a relative position between the position of an anatomical structure in each medical image of the second plurality of patients and the position of its associated label, and the learning algorithm determines the relative position based on the transformed statistical distribution data. Then, the relation between the image representation of the anatomical body part in the individual medical image and the label to be associated with the image representation of the anatomical body part in the individual medical image is a relative position between the position of the image representation of the anatomical body part in the individual medical image and the position of the label to be associated with the image representation of the anatomical body part in the individual medical image, and the learning algorithm determines the relative position based on the transformed statistics data.

In one example of the methods according to the third and fourth aspects, the learning algorithm may be a random forest algorithm. According to Antonio Criminisi, Jamie Shotton, Ender Konukoglu: “Decision Forests: A Unified Framework for Classification, Regression, Density Estimation, Manifold Learning and Semi-Supervised Learning” (2011), https://www.microsoft.com/en-us/research/wp-content/uploads/2016/02/CriminisiForests_FoundTrends_2011.pdf, random forests can be explained as follows:

Random forests or are an ensemble learning method for classification or regression that operates by constructing a multitude of decision trees at training time and outputting the class that is the mode of the classes (classification) or mean prediction (regression) of the individual trees.

The basic building block of a random forest is a single decision tree. A decision tree is a set of questions organized in a hierarchical manner and represented graphically as a tree. A decision tree estimates an unknown property (the “label”) of an object by asking successive questions about its known properties (the so-called “features”). Which question to ask next depends on the answer of the previous question and this relationship is represented graphically as a path through the tree which the object follows. The decision is then made based on the terminal node on the path (the so-called “leaf-node”). Each question corresponds to an internal node (so-called “split-node”) of the tree.

Each split node has associated to it a so-called test function. We formulate a test function at a split node j as a function with binary outputs h(v,θ _(j)):

×

→{0,1},

where 0 and 1 can be interpreted as “false” and “true” respectively, θ_(j)∈

denotes the parameters of the test function at the j-th split node.

v thereby is the current object (“data point”) denoted by a vector v=(x₁, x₂, . . . , x_(d))∈

, where the components x_(i) represent some attributes of the data point (the features), all of which form the Feature space

.

In the simplest form, the test function is a linear model which selects one feature axis in the feature space and classifies each data point according to whether the value of the respective feature is below or above a learnable threshold. Other more complex, non-linear test functions are possible.

In order to train a decision tree, we use a set of training data points for which both the features as well as the desired label are known. The goal of the training is to automatically learn suitable test functions at all the split-nodes which are best suited to determine the label from the features of a data point. Later on, such a trained decision tree can then be evaluated for a new data point with unknown label by sending the data point through the trained tree based on its features.

For understanding the training procedure, it is useful to denote subsets of training points as being associated with different tree branches. For instance S₁ denotes the subset of training points reaching node 1 (nodes are numbered in breadth-first order starting from 0 for the root F, and S₁ ^(L), S₁ ^(R) denote the subsets going to the left and to the right children of node 1, respectively.

The training takes care of selecting the type and parameters of the test function h(v, θ_(j)) associated with each split node (indexed by j) by optimizing a chosen objective function defined on an available training set.

The optimization of the split functions proceeds in a greedy manner. At each node j, depending on the subset of the incoming training set S_(j) we learn the function that “best” splits S_(j) into S_(j) ^(R) and S_(j) ^(L). This problem is formulated as the maximization of an objective function at that node Θ_(j) *=

I _(j); with I _(j) =I(S _(j) ,S _(j) ^(L) ,S _(j) ^(R),θ_(j)) S _(j) ^(L)={(v,y)∈S _(j) |h(v,θ _(j))=0} S _(j) ^(R)={(v,y)∈S _(j) |h(v,θ _(j))=1}

As before, the symbols S_(j), S_(j) ^(L), S_(j) ^(R) denote the sets of training points before and after the spit. The objective function is of an abstract form here. Its precise definition and the meaning of “best” depends on the task at hand (e.g., supervised or not, continuous or discrete output). For instance, for binary classification, the term “best” can be defined as splitting the training subset S_(k) such that the resulting child nodes are as pure as possible, that is, containing only training points of a single class. In this case the objective function can, for instance, be defined as the information gain.

During training we also need to optimize the tree structure (shape). Training starts at the root node, j=0, where the optimum split parameters are found as described earlier. Thus, we construct two child nodes, each receiving a different disjoint subset of the training set. This procedure is then applied to all the newly constructed nodes and the training phase continues. The structure of the tree depends on how and when we decide to stop growing various branches of the tree. Diverse stopping criteria can be applied. For example, it is common to stop the tree when a maximum number of levels D has been reached. Alternatively, one can impose a minimum value of the maximum max_(θ) _(j) I_(j), in other words we stop when the sought for attributes of the training points within the leaf nodes are similar to one another. Tree growing may also be stopped when a node contains too few training points. Avoiding growing full trees has been demonstrated to have positive effects in terms of generalization.

During training, randomness is injected into the trees: Instead of optimizing over the whole parameter space of the test functions, when training at the j-th node we only make available a small random subset

_(j)∈

of parameter values. Thus, under the randomness model training a tree is achieved by optimizing each split node j by Θ_(j) *=

I _(j),

Due to this randomized setup, multiple decision trees can later be trained in parallel, each exploiting a different set of properties from a data point.

At the end of the training phase we obtain: (i) the (greedily) optimum weak learners associated with each node, (ii) a learned tree structure, and (iii) a different set of training points at each leaf.

After training, each leaf node remains associated with a subset of (labelled) training data. During testing, a previously unseen point traverses the tree until it reaches a leaf.

Since the split nodes act on features, the input test point is likely to end up in a leaf associated with training points which are all similar to itself. Thus, it is reasonable to assume that the associated label must also be similar to that of the training points in that leaf. This justifies using the label statistics gathered in that leaf to predict the label associated with the input test point.

In the most general sense the leaf statistics can be captured using the posterior distributions p(c|v) and p(y|v),

where c and y represent the discrete or continuous labels, respectively. v is the data point that is tested in the tree and the conditioning denotes the fact that the distributions depend on the specific leaf node reached by the test point. Different leaf predictors can be used. For instance, a Maximum A-Posteriori (MAP) estimate may be obtained as c*=arg max_(c)p(c|v), in the discrete case.

Based on the above construction principle for decision trees, we can now proceed to decision forests, also called random forests:

A random decision forest is an ensemble of randomly trained decisions trees. The key aspect of the forest model is the fact that its component trees are all randomly different from one another. This leads to decorrelation between the individual tree predictions and, in turn, results in improved generalization and robustness.

In a forest with T trees we use the variable t

{1, . . . , T} to index each component tree. All trees are trained independently (and possibly in parallel). During testing, each test point v is simultaneously pushed through all trees (starting at the root) until it reaches the corresponding leaves. Tree testing can also often be done in parallel, thus achieving high computational efficiency on modern parallel CPU or GPU hardware. Combining all tree predictions into a single forest prediction may be done by a simple averaging operation. For instance, in classification

${{p\left( {c❘v} \right)} = {\frac{1}{T}{\sum\limits_{t = 1}^{T}{p_{t}\left( {c❘v} \right)}}}},$ where p_(t)(c|v) denotes the posterior distribution obtained by the t-th tree. Alternatively, one could also multiply the tree outputs together (though the trees are not statistically independent)

${p\left( {c❘v} \right)} = {\frac{1}{Z}{\sum\limits_{t = 1}^{T}{{Pt}\left( {c❘v} \right)}}}$

with the partition function Z ensuring probabilistic normalization.

In one example of the methods according to the first, second and third aspects, the learning algorithm may be a convolutional neural network. In the following, an explanation of convolutional neural networks as an example of the machine learning algorithm to be used with the disclosed invention is provided with reference to FIG. 1 .

Convolutional networks, also known as convolutional neural networks, or CNNs, are an example of neural networks for processing data that has a known grid-like topology. Examples include time-series data, which can be thought of as a 1-D grid taking samples at regular time intervals, and image data, which can be thought of as a 2-D or 3-D grid of pixels. The name “convolutional neural network” indicates that the network employs the mathematical operation of convolution. Convolution is a linear operation. Convolutional networks are simply neural networks that use convolution in place of general matrix multiplication in at least one of their layers. There are several variants on the convolution function that are widely used in practice for neural networks. In general, the operation used in a convolutional neural network does not correspond precisely to the definition of convolution as used in other fields, such as engineering or pure mathematics.

The main component of convolutional neural networks are artificial neurons. FIG. 1 is an example of a single neuron depicted. The node in the middle represents a neuron, which takes all inputs (x₁, . . . , x_(n)) and multiplies them with their specific weights (w₁, . . . , w_(n)) The importance of the input depends on the value of its weight. The addition of these computed values is called weighted sum which will be inserted into an activation function. The weighted sum z is defined as:

$\begin{matrix} {z = {{\sum}_{i = 0}^{n}{x_{i} \cdot w_{i}}}} & (1) \end{matrix}$

The bias b is an input-independent value which modifies the boundaries of the threshold. The resulting value is processed by an activation function which decides whether the input will be transferred to the next neuron.

A CNN usually takes an order 1 or 3 tensor as its input, e.g., an image with H rows, W columns, and 1 or 3 channels (R, G, B colour channels). Higher order tensor inputs, however, can be handled by CNN in a similar fashion. The input then sequentially goes through a series of processing. One processing step is usually called a layer, which could be a convolution layer, a pooling layer, a normalization layer, a fully connected layer, a loss layer, etc. Details of the layers are described in the sections below.

The above equation 5 illustrates how a CNN runs layer by layer in a forward pass. The input is x¹, usually an image (order 1 or 3 tensor). We note the parameters involved in the processing of the first layer collectively as a tensor w^(i). The output of the first layer is x², which also acts as the input to the second layer processing. This processing proceeds until processing of all layers in the CNN has been finished, which outputs x^(L). One additional layer, however, is added for backward error propagation, a method that learns good parameter values in the CNN. Suppose the problem at hand is an image classification problem with C classes. A commonly used strategy is to output x^(L) as a C-dimensional vector, the i-th entry of which encodes the prediction (posterior probability that x¹ comes from the i-th class). To make x^(L) a probability mass function, we can set the processing in the (L−1)-th layer as a softmax transformation of x^(L-1). In other applications, the output x^(L) may have other forms and interpretations. The last layer is a loss layer. Let us suppose t is the corresponding target (ground-truth) value for the input x¹, then a cost or loss function can be used to measure the discrepancy between the CNN prediction x^(L) and the target t. Note that some layers may not have any parameters, that is, w^(i) may be empty for some i.

In an example of a CNN, ReLu is used as an activation function for the convolutional layers and the softmax activation function provides information in order to give a classification output. The following sections will explain the purpose of the most important layers.

An input image is input to a feature learning section of a layer comprising convolution and ReLu, followed by a layer comprising pooling, which is followed by further pairwise repetitions of layers of convolution and ReLu and of pooling. The output of the feature learning section is input to a classification section which comprises layers directed to flattening, fully connecting and softmaxing.

In a convolutional layer, multiple convolution kernels are usually used. Assuming D kernels are used and each kernel is of spatial span H×W, we denote all the kernels as f. f is an order 4 tensor in

^(H×W×D) ^(l) _(×D). Similarly, we use index variables 0≤i<H, 0≤j<W, 0≤d^(l)<D^(l) and 0≤d<D to pinpoint a specific element in the kernels. Also note that the set of kernels f refers to the same object as the notation w^(L) above. We change the notation a bit to simplify the derivation. It is also clear that even if the mini-batch strategy is used, the kernels remain unchanged.

The spatial extent of the output is smaller than that of the input so long as the convolution kernel is larger than 1×1. Sometimes we need the input and output images to have the same height and width, and a simple padding trick can be used. For every channel of the input, if we pad (i.e., insert)

$\left\lfloor \frac{H - 1}{2} \right\rfloor$ rows above the first row and

$\left\lfloor \frac{H}{2} \right\rfloor$ rows below the last row, and pad

$\left\lfloor \frac{W - 1}{2} \right\rfloor$ columns the left of the first column and

$\left\lfloor \frac{W}{2} \right\rfloor$ columns to the right of the last column of the input, the convolution output will be H^(l)×W^(l)×D in size, i.e. having the same spatial extent as the input. └*┘ is the floor function. Elements of the padded rows and columns are usually set to 0, but other values are also possible.

Stride is another important concept in convolution. A kernel is convolved with the input at every possible spatial location, which corresponds to the stride s=1. However, if s>1, every movement of the kernel skip s−1 pixel locations (i.e., the convolution is performed once every s pixel both horizontally and vertically).

In this section, we consider the simple case when the stride is 1 and no padding is used. Hence, we have y (or x^(i+1)) in

^(H) ^(l+1) ^(×W) ^(l+1) ^(×D) ^(l) , with H^(l+1)=H^(l)−H+1, W^(l+1)=W^(l)−W+1, and D^(l+1)=D. In precise mathematics, the convolution procedure can be expressed as an equation:

$\begin{matrix} {y_{i^{l + 1},j^{l + 1},d} = {{\sum}_{i = 0}^{H}{\sum}_{j = 0}^{W}{\sum}_{d^{l} = 0}^{D^{l}}f_{i,j,d^{l},d} \times x_{{i^{l + 1} + i},{j^{l + 1} + j},d^{l}}^{l}}} & (2) \end{matrix}$

Equation 2 is repeated for all 0≤d≤D=D^(l+1), and for any spatial location (i^(l*1),j^(l+1)) satisfying 0≤i^(l+1)<H^(l)−H+1=H^(l+l), 0≤j^(l+1)<W^(l)−W+1=W^(l+1). In this equation, x_(i) _(l+1) _(+i,j) _(l+1) _(+j,d) _(l) ^(l) refers to the element of x^(l) indexed by the triplet (i^(l+1)+i,j^(l+1)+j,d^(l)). A bias term b_(d) is usually added to y_(i) _(l+1) _(,j) _(l+1) _(,d). We omit this term in this note for clearer presentation.

A pooling function replaces the output of the net at a certain location with a summary statistic of the nearby outputs. For example, a max pooling operation reports the maximum output within a rectangular neighbourhood of a table. Other popular pooling functions include the average of a rectangular neighbourhood, the L₂ norm of a rectangular neighbourhood, or a weighted average based on the distance from the central pixel. In all cases, pooling helps to make the representation approximately invariant to small translations of the input. Invariance to translation means that if we translate the input by a small amount, the values of the pooled outputs do not change. Because pooling summarizes the responses over a whole neighbourhood, it is possible to use fewer pooling units than detector units, by reporting summary statistics for pooling regions spaced k pixels apart rather than one pixel apart. This improves the computational efficiency of the network because the next layer has roughly k times fewer inputs to process.

Suppose all the parameters of a CNN model w¹, . . . , w^(L-1) have been learned, then we are ready to use this model for prediction. Prediction only involves running the CNN model forward, i.e., in the direction of the arrows in equation 1. Take the image classification problem as an example. Starting from the input x¹, we make it pass the processing of the first layer (the box with parameters w¹), and get x². In turn, x² is passed into the second layer, etc. Finally, we receive x^(l)∈

^(C), which estimates the posterior probabilities of x¹ belonging to the C categories. We can output the CNN prediction as: arg max_(i) x _(i) ^(L)  (3) Now, the problem is: how do we learn the model parameters?

As in many other learning systems, the parameters of a CNN model are optimized to minimize the loss z, i.e. we want the prediction of a CNN model to match the ground-truth labels. Suppose one training example x¹ is given for training such parameters. The training process involves running the CNN network in both directions. We first run the network in the forward pass to get x^(L) to achieve a prediction using the current CNN parameters. Instead of outputting a prediction, we need to compare the prediction with the target t corresponding to x¹, i.e. continue running the forward pass till the last loss layer. Finally, we achieve a loss z. The loss z is then a supervision signal, guiding how the parameters of the model should be modified (updated).

There exist several algorithms for optimizing a loss function and CNNs are not limited to a specific one. An example algorithm is called Stochastic Gradient Descent (SGD). This means the parameters are updated by using the gradient estimated from a (usually) small subset of training examples.

$\begin{matrix} \left. w^{i}\leftarrow{w^{i} - {\eta\frac{\delta z}{\delta w^{i}}}} \right. & (4) \end{matrix}$

In equation 4, the ←− sign implicitly indicates that the parameters w^(i) (of the i-layer) are updated from time t to t+1. If a time index t is explicitly used, this equation will look like

$\begin{matrix} {\left( w^{i} \right)^{t + 1} = {\left( w^{i} \right)^{t} - {\eta\frac{\delta z}{{\delta\left( w^{i} \right)}^{t}}}}} & (5) \end{matrix}$

In equation 4, the partial derivative

$\frac{\delta z}{\delta w^{i}}$ measures the rate of increase of z with respect to the changes in different dimensions of w^(i). This partial derivative vector is called the gradient in mathematical optimization. Hence, in a small local region around the current value of w^(i), to move w^(i) in the direction determined by the gradient will increase the objective value z. In order to minimize the loss function, we should update w^(i) along the opposite direction of the gradient. This updating rule is called the gradient descent.

If we move too far in the negative gradient direction, however, the loss function may increase. Hence, in every update we only change the parameters by a small proportion of the negative gradient, controlled by r (the learning rate). η>0 is usually set to a small number (e.g., η=0.001). One update based on x¹ will make the loss smaller for this particular training example if the learning rate is not too large. However, it is very possible that it will make the loss of some other training examples become larger. Hence, we need to update the parameters using all training examples. When all training examples have been used to update the parameters, we say one epoch has been processed. One epoch will in general reduce the average loss on the training set until the learning system overfits the training data. Hence, we can repeat the gradient descent updating epochs and terminate at some point to obtain the CNN parameters (e.g., we can terminate when the average loss on a validation set increases).

The last layer's partial derivatives are easy to compute. Because x^(L) is connected to z directly under the control of parameters w^(L), it is easy to compute

$\frac{\delta z}{\delta w^{L}}.$ This step is only needed when w^(L) is not empty. In the same spirit, it is also easy to compute

$\frac{\delta z}{\delta w^{L}}.$ For example, if the squared L₂ loss is used, we have an empty

$\frac{\delta z}{\delta w^{L}},{{{and}\frac{\delta z}{\delta x^{L}}} = {x^{L} - {t.}}}$

In fact, for every layer, we compute two sets of gradients: the partial derivatives of z with respect to the layer parameters w^(i), and that layer's input x_(i). The term

$\frac{\delta z}{\delta w^{i}},$ as seen in Equation 4, can be used to update the current (i-th) layer's parameters. The term

$\frac{\delta z}{\delta x^{i}}$ can be used to update parameters backwards, e.g., to the (i−1)-th layer. An intuitive explanation is: x_(i) is the output of the (i−1)-th layer and

$\frac{\delta z}{\delta x^{i}}$ is how x^(i) should be changed to reduce the loss function. Hence, we could view

$\frac{\delta z}{\delta x^{i}}$ as the part of the “error” supervision information propagated from z backward till the current layer, in a layer by layer fashion. Thus, we can continue the back propagation process, and use

$\frac{\delta z}{\delta x^{i}}$ to propagate the errors backward to the (i−1)-th layer. This layer-by-layer backward updating procedure makes learning a CNN much easier.

Take the i-th layer as an example. When we update the i-th layer, the back propagation process for the (i+1)-th layer must have been finished. That is, we already computed the terms

$\frac{\delta z}{\delta w^{i + 1}}{and}{\frac{\delta z}{\delta x^{i + 1}}.}$ Both are stored in memory and ready for use. Now our task is to compute

$\frac{\delta z}{\delta w^{i}}{and}{\frac{\delta z}{\delta x^{i}}.}$ Using the chain rule, we have

${\frac{\partial z}{\partial\left( {{vec}\left( w^{i} \right)}^{T} \right)} = {\frac{\partial z}{\left. {\partial{{vec}\left( x^{i + 1} \right)}^{T}} \right)}\frac{\partial{{vec}\left( x^{i + 1} \right)}}{\partial\left( {{vec}\left( w^{i} \right)}^{T} \right)}}}{\frac{\partial z}{\partial\left( {{vec}\left( x^{i} \right)}^{T} \right)} = {\frac{\partial z}{\partial\left( {{vec}\left( x^{i + 1} \right)}^{T} \right)}\frac{\partial{{vec}\left( x^{i + 1} \right)}}{\partial\left( {{vec}\left( x^{i} \right)}^{T} \right)}}}$

Since

$\frac{\partial z}{\partial x^{i + 1}}$ is already computed and stored in memory, it requires just a matrix reshaping operation (vec) and an additional transpose operation to get

$\frac{\partial z}{\partial{{vec}\left( x^{i + 1} \right)}},$ which is the first term in the right hand side (RHS) of both equations. So long as we can compute

${\frac{\partial{{vec}\left( x^{i + 1} \right)}}{\partial\left( {{vec}\left( w^{i} \right)}^{T} \right)}{and}\frac{\partial{{vec}\left( x^{i + 1} \right)}}{\partial\left( {{vec}\left( x^{i} \right)}^{T} \right)}},$ we can easily get what we want (the left hand side of both equations).

$\frac{\partial{{vec}\left( x^{i + 1} \right)}}{\partial\left( {{vec}\left( w^{i} \right)}^{T} \right)}{and}\frac{\partial{{vec}\left( x^{i + 1} \right)}}{\partial\left( {{vec}\left( x^{i} \right)}^{T} \right)}$ are much easier to compute than directly computing

${\frac{\partial z}{\partial\left( {{vec}\left( w^{i} \right)}^{T} \right)}{and}\frac{\partial z}{\partial\left( {{vec}\left( x^{i} \right)}^{T} \right)}},$ because x^(i) is directly related to x^(i+1), through a function with parameters w^(i).

In the context of neural networks, activations serve as transfer functions between the input of a neuron and the output. They define under which conditions the node is activated, i.e. the input values are mapped to the output which, in hidden layers, serves again as one of the inputs to the succeeding neuron. There exists a vast amount of different activation functions with different characteristics.

A loss function quantifies how well an algorithm models the given data. To learn from the data and in order to change the weights of the network, the loss function has to be minimized. Generally, one can make the distinction between a regression loss and classification loss. Classification predicts output from set of finite categorical values (class labels), and regression, on the other hand, deals with prediction a continuous value.

In the following mathematical formulations, the following parameters are defined as:

-   -   n is the number of training examples     -   i is the i-th training example in a data set     -   y_(i) is the ground truth label for the i-th training example     -   ŷ_(i) is the prediction for i-th training example

The most common setting for classification problems is cross-entropy loss. It increases as the predicted probability diverges from the actual label. The log of the actual predicted probability is multiplied with the ground truth class. An important aspect of this is that cross entropy loss penalizes heavily the predictions that are confident but wrong. The mathematical formulation can be described as: CrossEntropyLoss=−(y _(i) log(ŷ _(i))+(1−y _(i))log(1−

))  (6)

A typical example for a regression loss is the mean square error or L₂ loss. As the name suggests, mean square error is measured as the average of the squared difference between predictions and actual observations. It is only concerned with the average magnitude of error irrespective of their direction. However, due to squaring, predictions which are far away from actual values are penalized heavily in comparison to less deviated predictions. Plus MSE has nice mathematical properties which makes it easier to calculate gradients. Its formulation is as follows:

${MSE} = {\frac{1}{n} \cdot {\sum\limits_{i = 1}^{n}\left( {y_{i} -} \right)^{2}}}$

The following documents contain information on the functioning of convolutional neural networks:

-   I. Goodfellow, Y. Bengio, and A. Courville, “Deep learning, chapter     convolutional networks.” http://www.deeplearningbook.org, 2016. -   J. Wu, “Introduction to convolutional neural networks.”     https://pdfs.semanticscholar.org/450c/a19932fcef1ca6d0442cbf52fec38fb9d1e5.pdf. -   “Common loss functions in machine learning.”     https://towardsdatascience.com/common-loss-functions-in-machine-learning-46af0ffc4d23.     Accessed: 2019-08-22. -   Alex Krizhevsky, Ilya Sutskever, and Geoffrey E. Hinton, “Imagenet     classification with deep convolutional neural networks.”     http://papers.nips.cc/paper/4824-imagenet-classification-with-deep-convolutional-neural-networks.pdf. -   S. Ren, K. He, R. Girshick, and J. Sun, “Faster r-cnn: Towards     real-time object detection with region proposal networks.”     https://arxiv.org/pdf/1506.01497.pdf. -   S.-E. Wei, V. Ramakrishna, T. Kanade, and Y. Sheikh, “Convolutional     pose machines.” https://arxiv.org/pdf/1602.00134.pdf. -   Jonathan Long, Evan Shelhamer, and Trevor Darrell, “Fully     convolutional networks for semantic segmentation.”     https://www.cv-foundation.org/openaccess/content_cvpr_2015/papers/Long_Fully_Convolutional_Networks_2015_CVPR_paper.pdf.

In a fifth aspect, the invention is directed to a program which, when running on a computer or when loaded onto a computer, causes the computer to perform the method steps of the method according to the first, second, third or fourth aspect, and/or a program storage medium on which the program is stored or a program storage medium on which data defining the model parameters and the architecture of a learning algorithm which has been trained by executing the method according to the third aspect is stored, and/or a data carrier signal carrying the aforementioned program, and/or a data carrier signal carrying data defining the model parameters and the architecture of a learning algorithm which has been trained by executing the method according to the third aspect, and/or a data stream which carries the aforementioned program, and/or a data stream which carries data defining the model parameters and the architecture of a learning algorithm which has been trained by executing the method according to the third aspect, and/or at least one computer comprising at least one processor and a memory, wherein the aforementioned program is running on the at least one processor or loaded into the memory of the computer.

The invention may alternatively or additionally relate to a (physical, for example electrical, for example technically generated) signal wave, for example a digital signal wave, such as an electromagnetic carrier wave carrying information which represents the program, for example the aforementioned program, which for example comprises code means which are adapted to perform any or all of the steps of the method according to the first aspect. The signal wave is in one example a data carrier signal carrying the aforementioned computer program. A computer program stored on a disc is a data file, and when the file is read out and transmitted it becomes a data stream for example in the form of a (physical, for example electrical, for example technically generated) signal. The signal can be implemented as the signal wave, for example as the electromagnetic carrier wave which is described herein. For example, the signal, for example the signal wave is constituted to be transmitted via a computer network, for example LAN, WLAN, WAN, mobile network, for example the internet. For example, the signal, for example the signal wave, is constituted to be transmitted by optic or acoustic data transmission. The invention according to the second aspect therefore may alternatively or additionally relate to a data stream representative of the aforementioned program, i.e. comprising the program.

In a sixth aspect, the invention is directed to a medical data processing system, comprising:

-   a) the at least one computer according to the fifth aspect, wherein     the program causes the computer to perform the method steps of the     method according to the first or second aspect; -   b) at least one electronic data storage device storing the initial     segmented patient image data and the segmentation correction data;     and -   c) the program storage medium according to the fifth aspect,

wherein the at least one computer is operably coupled to the at least one electronic data storage device for acquiring, from the at least one electronic data storage device, the initial segmented patient image data and the segmentation correction data, and for storing, in the at least one electronic data storage device, at least the combined correction data and, as far as the program causes the computer to perform the method steps of the method according to the second aspect, the corrected segmented patient image data.

In a seventh aspect, the invention is directed to a medical data processing system, comprising:

-   a) the at least one computer according to the fifth aspect, wherein     the program causes the computer to perform the method steps of the     method according to any one of claims the fourth aspect; -   b) at least one electronic data storage device storing the     individual patient image data; -   c) the program storage medium according to the fifth aspect,     -   wherein the at least one computer is operably coupled to     -   the at least one electronic data storage device for acquiring,         from the at least one electronic data storage device, the         individual patient image data, and for storing, in the at least         one electronic data storage device, at least the segmented         individual patient image data; and     -   the program storage medium for acquiring, from the program         storage medium, the data defining the model parameters and the         architecture of the learning algorithm.

Definitions

In this section, definitions for specific terminology used in this disclosure are offered which also form part of the present disclosure.

The method in accordance with the invention is for example a computer implemented method. For example, all the steps or merely some of the steps (i.e. less than the total number of steps) of the method in accordance with the invention can be executed by a computer (for example, at least one computer). An embodiment of the computer implemented method is a use of the computer for performing a data processing method. An embodiment of the computer implemented method is a method concerning the operation of the computer such that the computer is operated to perform one, more or all steps of the method.

The computer for example comprises at least one processor and for example at least one memory in order to (technically) process the data, for example electronically and/or optically. The processor being for example made of a substance or composition which is a semiconductor, for example at least partly n- and/or p-doped semiconductor, for example at least one of II-, III-, IV-, V-, VI-semiconductor material, for example (doped) silicon and/or gallium arsenide. The calculating or determining steps described are for example performed by a computer. Determining steps or calculating steps are for example steps of determining data within the framework of the technical method, for example within the framework of a program. A computer is for example any kind of data processing device, for example electronic data processing device. A computer can be a device which is generally thought of as such, for example desktop PCs, notebooks, netbooks, etc., but can also be any programmable apparatus, such as for example a mobile phone or an embedded processor. A computer can for example comprise a system (network) of “sub-computers”, wherein each sub-computer represents a computer in its own right. The term “computer” includes a cloud computer, for example a cloud server. The term computer includes a server resource. The term “cloud computer” includes a cloud computer system which for example comprises a system of at least one cloud computer and for example a plurality of operatively interconnected cloud computers such as a server farm. Such a cloud computer is preferably connected to a wide area network such as the world wide web (VWWV) and located in a so-called cloud of computers which are all connected to the world wide web. Such an infrastructure is used for “cloud computing”, which describes computation, software, data access and storage services which do not require the end user to know the physical location and/or configuration of the computer delivering a specific service. For example, the term “cloud” is used in this respect as a metaphor for the Internet (world wide web). For example, the cloud provides computing infrastructure as a service (IaaS). The cloud computer can function as a virtual host for an operating system and/or data processing application which is used to execute the method of the invention. The cloud computer is for example an elastic compute cloud (EC2) as provided by Amazon Web Services™. A computer for example comprises interfaces in order to receive or output data and/or perform an analogue-to-digital conversion. The data are for example data which represent physical properties and/or which are generated from technical signals. The technical signals are for example generated by means of (technical) detection devices (such as for example devices for detecting marker devices) and/or (technical) analytical devices (such as for example devices for performing (medical) imaging methods), wherein the technical signals are for example electrical or optical signals. The technical signals for example represent the data received or outputted by the computer. The computer is preferably operatively coupled to a display device which allows information outputted by the computer to be displayed, for example to a user. One example of a display device is a virtual reality device or an augmented reality device (also referred to as virtual reality glasses or augmented reality glasses) which can be used as “goggles” for navigating. A specific example of such augmented reality glasses is Google Glass (a trademark of Google, Inc.). An augmented reality device or a virtual reality device can be used both to input information into the computer by user interaction and to display information outputted by the computer. Another example of a display device would be a standard computer monitor comprising for example a liquid crystal display operatively coupled to the computer for receiving display control data from the computer for generating signals used to display image information content on the display device. A specific embodiment of such a computer monitor is a digital lightbox. An example of such a digital lightbox is Buzz®, a product of Brainlab AG. The monitor may also be the monitor of a portable, for example handheld, device such as a smart phone or personal digital assistant or digital media player.

The invention also relates to a computer program comprising instructions which, when on the program is executed by a computer, cause the computer to carry out the method or methods, for example, the steps of the method or methods, described herein and/or to a computer-readable storage medium (for example, a non-transitory computer-readable storage medium) on which the program is stored and/or to a computer comprising said program storage medium and/or to a (physical, for example electrical, for example technically generated) signal wave, for example a digital signal wave, such as an electromagnetic carrier wave carrying information which represents the program, for example the aforementioned program, which for example comprises code means which are adapted to perform any or all of the method steps described herein. The signal wave is in one example a data carrier signal carrying the aforementioned computer program. The invention also relates to a computer comprising at least one processor and/or the aforementioned computer-readable storage medium and for example a memory, wherein the program is executed by the processor.

Within the framework of the invention, computer program elements can be embodied by hardware and/or software (this includes firmware, resident software, micro-code, etc.). Within the framework of the invention, computer program elements can take the form of a computer program product which can be embodied by a computer-usable, for example computer-readable data storage medium comprising computer-usable, for example computer-readable program instructions, “code” or a “computer program” embodied in said data storage medium for use on or in connection with the instruction-executing system. Such a system can be a computer; a computer can be a data processing device comprising means for executing the computer program elements and/or the program in accordance with the invention, for example a data processing device comprising a digital processor (central processing unit or CPU) which executes the computer program elements, and optionally a volatile memory (for example a random access memory or RAM) for storing data used for and/or produced by executing the computer program elements. Within the framework of the present invention, a computer-usable, for example computer-readable data storage medium can be any data storage medium which can include, store, communicate, propagate or transport the program for use on or in connection with the instruction-executing system, apparatus or device. The computer-usable, for example computer-readable data storage medium can for example be, but is not limited to, an electronic, magnetic, optical, electromagnetic, infrared or semiconductor system, apparatus or device or a medium of propagation such as for example the Internet. The computer-usable or computer-readable data storage medium could even for example be paper or another suitable medium onto which the program is printed, since the program could be electronically captured, for example by optically scanning the paper or other suitable medium, and then compiled, interpreted or otherwise processed in a suitable manner. The data storage medium is preferably a non-volatile data storage medium. The computer program product and any software and/or hardware described here form the various means for performing the functions of the invention in the example embodiments. The computer and/or data processing device can for example include a guidance information device which includes means for outputting guidance information. The guidance information can be outputted, for example to a user, visually by a visual indicating means (for example, a monitor and/or a lamp) and/or acoustically by an acoustic indicating means (for example, a loudspeaker and/or a digital speech output device) and/or tactilely by a tactile indicating means (for example, a vibrating element or a vibration element incorporated into an instrument). For the purpose of this document, a computer is a technical computer which for example comprises technical, for example tangible components, for example mechanical and/or electronic components. Any device mentioned as such in this document is a technical and for example tangible device.

The expression “acquiring data” for example encompasses (within the framework of a computer implemented method) the scenario in which the data are determined by the computer implemented method or program. Determining data for example encompasses measuring physical quantities and transforming the measured values into data, for example digital data, and/or computing (and e.g. outputting) the data by means of a computer and for example within the framework of the method in accordance with the invention. A step of “determining” as described herein for example comprises or consists of issuing a command to perform the determination described herein. For example, the step comprises or consists of issuing a command to cause a computer, for example a remote computer, for example a remote server, for example in the cloud, to perform the determination. Alternatively or additionally, a step of “determination” as described herein for example comprises or consists of receiving the data resulting from the determination described herein, for example receiving the resulting data from the remote computer, for example from that remote computer which has been caused to perform the determination. The meaning of “acquiring data” also for example encompasses the scenario in which the data are received or retrieved by (e.g. input to) the computer implemented method or program, for example from another program, a previous method step or a data storage medium, for example for further processing by the computer implemented method or program. Generation of the data to be acquired may but need not be part of the method in accordance with the invention. The expression “acquiring data” can therefore also for example mean waiting to receive data and/or receiving the data. The received data can for example be inputted via an interface. The expression “acquiring data” can also mean that the computer implemented method or program performs steps in order to (actively) receive or retrieve the data from a data source, for instance a data storage medium (such as for example a ROM, RAM, database, hard drive, etc.), or via the interface (for instance, from another computer or a network). The data acquired by the disclosed method or device, respectively, may be acquired from a database located in a data storage device which is operably to a computer for data transfer between the database and the computer, for example from the database to the computer. The computer acquires the data for use as an input for steps of determining data. The determined data can be output again to the same or another database to be stored for later use. The database or database used for implementing the disclosed method can be located on network data storage device or a network server (for example, a cloud data storage device or a cloud server) or a local data storage device (such as a mass storage device operably connected to at least one computer executing the disclosed method). The data can be made “ready for use” by performing an additional step before the acquiring step. In accordance with this additional step, the data are generated in order to be acquired. The data are for example detected or captured (for example by an analytical device). Alternatively or additionally, the data are inputted in accordance with the additional step, for instance via interfaces. The data generated can for example be inputted (for instance into the computer). In accordance with the additional step (which precedes the acquiring step), the data can also be provided by performing the additional step of storing the data in a data storage medium (such as for example a ROM, RAM, CD and/or hard drive), such that they are ready for use within the framework of the method or program in accordance with the invention. The step of “acquiring data” can therefore also involve commanding a device to obtain and/or provide the data to be acquired. In particular, the acquiring step does not involve an invasive step which would represent a substantial physical interference with the body, requiring professional medical expertise to be carried out and entailing a substantial health risk even when carried out with the required professional care and expertise. In particular, the step of acquiring data, for example determining data, does not involve a surgical step and in particular does not involve a step of treating a human or animal body using surgery or therapy. In order to distinguish the different data used by the present method, the data are denoted (i.e. referred to) as “XY data” and the like and are defined in terms of the information which they describe, which is then preferably referred to as “XY information” and the like.

Preferably, atlas data is acquired which describes (for example defines, more particularly represents and/or is) a general three-dimensional shape of the anatomical body part. The atlas data therefore represents an atlas of the anatomical body part. An atlas typically consists of a plurality of generic models of objects, wherein the generic models of the objects together form a complex structure. For example, the atlas constitutes a statistical model of a patient's body (for example, a part of the body) which has been generated from anatomic information gathered from a plurality of human bodies, for example from medical image data containing images of such human bodies. In principle, the atlas data therefore represents the result of a statistical analysis of such medical image data for a plurality of human bodies. This result can be output as an image—the atlas data therefore contains or is comparable to medical image data. Such a comparison can be carried out for example by applying an image fusion algorithm which conducts an image fusion between the atlas data and the medical image data. The result of the comparison can be a measure of similarity between the atlas data and the medical image data. The atlas data comprises image information (for example, positional image information) which can be matched (for example by applying an elastic or rigid image fusion algorithm) for example to image information (for example, positional image information) contained in medical image data so as to for example compare the atlas data to the medical image data in order to determine the position of anatomical structures in the medical image data which correspond to anatomical structures defined by the atlas data.

The human bodies, the anatomy of which serves as an input for generating the atlas data, advantageously share a common feature such as at least one of gender, age, ethnicity, body measurements (e.g. size and/or mass) and pathologic state. The anatomic information describes for example the anatomy of the human bodies and is extracted for example from medical image information about the human bodies. The atlas of a femur, for example, can comprise the head, the neck, the body, the greater trochanter, the lesser trochanter and the lower extremity as objects which together make up the complete structure. The atlas of a brain, for example, can comprise the telencephalon, the cerebellum, the diencephalon, the pons, the mesencephalon and the medulla as the objects which together make up the complex structure. One application of such an atlas is in the segmentation of medical images, in which the atlas is matched to medical image data, and the image data are compared with the matched atlas in order to assign a point (a pixel or voxel) of the image data to an object of the matched atlas, thereby segmenting the image data into objects.

For example, the atlas data includes information of the anatomical body part. This information is for example at least one of patient-specific, non-patient-specific, indication-specific or non-indication-specific. The atlas data therefore describes for example at least one of a patient-specific, non-patient-specific, indication-specific or non-indication-specific atlas. For example, the atlas data includes movement information indicating a degree of freedom of movement of the anatomical body part with respect to a given reference (e.g. another anatomical body part). For example, the atlas is a multimodal atlas which defines atlas information for a plurality of (i.e. at least two) imaging modalities and contains a mapping between the atlas information in different imaging modalities (for example, a mapping between all of the modalities) so that the atlas can be used for transforming medical image information from its image depiction in a first imaging modality into its image depiction in a second imaging modality which is different from the first imaging modality or to compare (for example, match or register) images of different imaging modality with one another.

In the field of medicine, imaging methods (also called imaging modalities and/or medical imaging modalities) are used to generate image data (for example, two-dimensional or three-dimensional image data) of anatomical structures (such as soft tissues, bones, organs, etc.) of the human body. The term “medical imaging methods” is understood to mean (advantageously apparatus-based) imaging methods (for example so-called medical imaging modalities and/or radiological imaging methods) such as for instance computed tomography (CT) and cone beam computed tomography (CBCT, such as volumetric CBCT), x-ray tomography, magnetic resonance tomography (MRT or MRI), conventional x-ray, sonography and/or ultrasound examinations, and positron emission tomography. For example, the medical imaging methods are performed by the analytical devices. Examples for medical imaging modalities applied by medical imaging methods are: X-ray radiography, magnetic resonance imaging, medical ultrasonography or ultrasound, endoscopy, elastography, tactile imaging, thermography, medical photography and nuclear medicine functional imaging techniques as positron emission tomography (PET) and Single-photon emission computed tomography (SPECT), as mentioned by Wikipedia.

The image data thus generated is also termed “medical imaging data”. Analytical devices for example are used to generate the image data in apparatus-based imaging methods. The imaging methods are for example used for medical diagnostics, to analyse the anatomical body in order to generate images which are described by the image data. The imaging methods are also for example used to detect pathological changes in the human body. However, some of the changes in the anatomical structure, such as the pathological changes in the structures (tissue), may not be detectable and for example may not be visible in the images generated by the imaging methods. A tumour represents an example of a change in an anatomical structure. If the tumour grows, it may then be said to represent an expanded anatomical structure. This expanded anatomical structure may not be detectable; for example, only a part of the expanded anatomical structure may be detectable. Primary/high-grade brain tumours are for example usually visible on MRI scans when contrast agents are used to infiltrate the tumour. MRI scans represent an example of an imaging method. In the case of MRI scans of such brain tumours, the signal enhancement in the MRI images (due to the contrast agents infiltrating the tumour) is considered to represent the solid tumour mass. Thus, the tumour is detectable and for example discernible in the image generated by the imaging method. In addition to these tumours, referred to as “enhancing” tumours, it is thought that approximately 10% of brain tumours are not discernible on a scan and are for example not visible to a user looking at the images generated by the imaging method.

Mapping describes a transformation (for example, linear transformation) of an element (for example, a pixel or voxel), for example the position of an element, of a first data set in a first coordinate system to an element (for example, a pixel or voxel), for example the position of an element, of a second data set in a second coordinate system (which may have a basis which is different from the basis of the first coordinate system). In one embodiment, the mapping is determined by comparing (for example, matching) the color values (for example grey values) of the respective elements by means of an elastic or rigid fusion algorithm. The mapping is embodied for example by a transformation matrix (such as a matrix defining an affine transformation).

BRIEF DESCRIPTION OF THE DRAWINGS

In the following, the invention is described with reference to the appended figures which give background explanations and represent specific embodiments of the invention.

The scope of the invention is however not limited to the specific features disclosed in the context of the figures, wherein

FIG. 1 illustrates a neuron of a (convolutional) neural network;

FIG. 2 illustrates the basic flow of the method according to the first aspect;

FIG. 3 illustrates the basic flow of the method according to the second aspect;

FIG. 4 illustrates the basic flow of the method according to the third aspect;

FIG. 5 illustrates the basic flow of the method according to the fourth aspect;

FIG. 6 shows a possible application of the methods according to the first to fourth aspect.

FIG. 7 is a schematic illustration of the systems according to the fifth and sixth aspect.

DESCRIPTION OF EMBODIMENTS

FIG. 1 illustrates the structure of a neuron as part of a (convolutional) neural network, in which input is assigned certain weights for processing by an activation function which generates the output of the neuron.

FIG. 2 describes the basic flow of the method according to the first aspect, which starts in step S21 with acquiring the initial segmented patient image data, continues to step S22 which encompasses acquisition of the segmentation correction data, and then proceeds to acquiring the atlas data in step S23. On that basis, step S24 calculates the correction transformation data, which is followed by determination of the transformed correction data in step S25. Finally, the combined correction data is determined in step S26.

FIG. 3 illustrates the basic steps of the method according to the second aspect, in which step S31 encompasses execution of the method according to the first aspect and step S32 relates to acquisition of the segmented individual patient image data. Step S33 comprises determination of the correction re-transformation data. Then, step S34 follows which determines the re-transformed correction data and step 35 then determines the corrected segmented patient image data.

FIG. 4 illustrates the basic steps of the method according to the third aspect, in which step S41 encompasses execution of the method according to the first or second aspect and step S42 relates to acquisition of the training patient image data. Subsequent step 43 acquires the label data, followed by determination of the transformed statistics data in step S44. Then, step S45 determines the statistics assignment data, and finally step S46 determines the label relation data.

FIG. 5 illustrates the basic steps of the method according to the fourth aspect, in which step S51 encompasses acquisition of the individual patient image data and subsequent step S52 determines the segmented individual patient image data.

FIG. 6 gives an overview of the application of the method according to the first to third aspect. In a first (correction) stage, the following steps are executed: Patient image data 1 is segmented initially by an algorithm 2 to generate segmented patient image data 3, e.g. to generate a label indicating the outline of an organ in the patient image data and then the segmented patient image data or the label are corrected 4, e.g. by a user. The corrections are stored in the form of spatial correction maps. The spatial correction maps are registered into a generic model (atlas) 5 and aggregated (combined), e.g. in a central repository storing the combined correction data 6. In a second (learning) stage, the following steps are executed: The combined correction data 6 are then input as weights 7, e.g. into a cost or loss function that compares the segmented patient image data 3 which serves as a prediction for the cost or loss function and the label 8 which is part of a segmentation learning algorithm 2, which, e.g. is identical to the segmentation algorithm used in the first stage. Additionally, patient data 1 and labels 8, e.g. manually generated outlines of an organ are input.

FIG. 7 is a schematic illustration of the medical system 61 according to the fifth or sixth aspect. The system is in its entirety identified by reference sign 61 and comprises a computer 62, an electronic data storage device (such as a hard disc) 63 for storing the data stored by the system according to the fifth or sixth, respectively, aspect. The components of the medical system 1 have the functionalities and properties explained above with regard to the fifth and sixth, respectively, aspects of this disclosure. 

What is claimed is:
 1. A computer-implemented method of determining corrections for correcting segmentation of medical image data, which includes a computer-implemented method of determining distributions of corrections for correcting the segmentation of medical image data comprising: acquiring initial segmented patient image data which describes an initial segmentation of digital medical images of an anatomical body part of a first plurality of patients; acquiring segmentation correction data which describes a correction of the initial segmentation for each patient of the first plurality of patients; acquiring atlas data which describes an image-based model of the anatomical body part; determining correction transformation data based on the segmentation correction data and the atlas data, wherein the correction transformation data describes a transformation for transforming the corrections into a reference system used for describing positions in the image-based model; determining transformed correction data based on the segmentation correction data and the correction transformation data by applying the transformation to the corrections to determine transformed corrections; determining combined correction data based on the transformed correction data, wherein the combined correction data describes the results of a statistical analysis of the corrections; wherein the computer-implemented method of determining corrections for correcting the segmentation of medical image data further comprises steps in which: segmented individual patient image data is acquired which describes a segmentation of the anatomical body part of the patient in a digital individual medical image; correction re-transformation data is determined based on the atlas data and the individual patient image data, wherein the correction re-transformation data describes a transformation for transforming the results of the statistical analysis of the corrections into the reference system used for describing positions in the digital individual medical image; re-transformed correction data is determined based on the combined correction data and the correction re-transformation data; and corrected segmented patient image data is determined based on the individual patient image data and the re-transformed correction data, wherein the corrected segmented patient image data describes a result of applying the corrections to the segmentation of the anatomical body part of the patient in the digital individual medical image.
 2. The method according to claim 1, wherein the result of applying the corrections to the segmentation of the anatomical body part of the patient in the digital individual medical image is determined by applying the corrections in dependence on a characteristic quantity of the result of the statistical analysis.
 3. The method according to claim 1, wherein the result of the statistical analysis constitutes a statistical distribution of the corrections for the first plurality of patients.
 4. The method according to claim 1, wherein the statistical analysis is an averaging analysis.
 5. The method according to claim 2, wherein the characteristic quantity is an arithmetic average, or a variance.
 6. The method according to claim 1, wherein the segmentation correction data is acquired based on user input.
 7. A computer-implemented method of training a learning algorithm for determining a connection of a segmentation of a digital medical image, the method comprising: executing a computer-implemented method of determining distributions of corrections for correcting a segmentation of medical image data which includes: acquiring initial segmented patient image data which describes an initial segmentation of digital medical images of an anatomical body part of a first plurality of patients; acquiring segmentation correction data which describes a correction of the initial segmentation for each patient of the first plurality of patients; acquiring atlas data which describes an image-based model of the anatomical body part; determining correction transformation data based on the segmentation correction data and the atlas data, wherein the correction transformation data describes a transformation for transforming the corrections into a reference system used for describing positions in the image-based model; determining transformed correction data based on the segmentation correction data and the correction transformation data by applying the transformation to the corrections to determine transformed corrections; determining combined correction data based on the transformed co2rection data, wherein the combined correction data describes the results of a statistical analysis of the corrections; wherein the computer-implemented method of determining corrections for correcting the segmentation of medical image data further comprises: acquiring training patient image data which describes digital medical images of an anatomical structure of a second plurality of patients; acquiring label data which describes positions of labels assigned to the training patient image data, wherein the positions of the labels are defined in the reference system in which positions in the training patient image data are defined; determining transformed statistical distribution data based on the training patient image data and the combined correction data, wherein the transformed statistical distribution data describes a result of transforming the statistical distributions into the reference system in which positions in the training patient image data are defined; determining statistics assignment data based on the transformed statistical distribution data and the label data, wherein the statistics assignment data describes an assignment of the results of the statistical analysis to the labels; and determining label relation data which describes model parameters of the learning algorithm for establishing a relation between the position of the anatomical structure in each medical image of the second plurality of patients and the position of its associated label, wherein the label relation data is determined by inputting the training patient image data and the label data and the transformed statistical distribution data into a function which establishes the relation.
 8. The method according to claim 7, wherein the relation between the position of the anatomical structure in each medical image of the second plurality of patients and the position of its associated label is defined as a relative position between the position of the anatomical structure in each medical image of the second plurality of patients and the position of its associated label, and wherein the learning algorithm determines the relative position based on the transformed statistical distributed data.
 9. The method according to claim 7, wherein the learning algorithm comprises or consists of a machine learning algorithm.
 10. The method according to claim 7, wherein the learning algorithm comprises or consists of a convolutional neural network.
 11. The method according to claim 7, wherein the model parameters define the learnable parameters, of the learning algorithm.
 12. A computer-implemented method of determining a relation between an image representation of an anatomical body part in an individual medical image and a label to be associated with the image representation of the anatomical body part in the individual medical image, the method comprising: executing a computer-implemented method of determining distributions of corrections for correcting a segmentation of medical image data which includes: acquiring initial segmented patient image data which describes an initial segmentation of digital medical images of the anatomical body part of a first plurality of patients; acquiring segmentation correction data which describes a correction of the initial segmentation for each patient of the first plurality of patients; acquiring atlas data which describes an image-based model of the anatomical body part; determining correction transformation data based on the segmentation correction data and the atlas data, wherein the correction transformation data describes a transformation for transforming the corrections into a reference system used for describing positions in the image-based model; determining transformed correction data based on the segmentation correction data and the correction transformation data by applying the transformation to the corrections to determine transformed corrections; determining combined correction data based on the transformed correction data, wherein the combined correction data describes a result of a statistical analysis of the corrections; wherein the computer-implemented method of determining corrections for correcting the segmentation of medical image data further includes: acquiring individual patient image data which describes a digital individual medical image describing the anatomical body part of a patient; and determining segmented individual patient image data which describes a relation between the image representation of the anatomical body part in the individual medical image and a label to be associated with the image representation of the anatomical body part in the individual medical image, wherein the segmented individual patient image data is determined by inputting the individual patient image data into a function learning algorithm which establishes the relation between the image representation of the anatomical body part in the individual medical image and a label to be associated with the image representation of the anatomical body part in the individual medical image, the function being part of a learning algorithm which has been trained by executing the method according to any one of the five immediately preceding claims.
 13. The method according to claim 12, wherein the relation between the image representation of the anatomical body part in the individual medical image and the label to be associated with the image representation of the anatomical body part in the individual medical image is a relative position between the position of the image representation of the anatomical body part in the individual medical image and the position of the label to be associated with the image representation of the anatomical body part in the individual medical image, and wherein the learning algorithm determines the relative position based on the transformed statistical distributed data.
 14. A non-transitory computer readable storage medium program comprising instructions which, when running on at least one computer, causes the at least one computer to perform the method steps of determining distributions of corrections for correcting a segmentation of medical image data which includes: acquiring initial segmented patient image data which describes an initial segmentation of digital medical images of an anatomical body part of a first plurality of patients; acquiring segmentation correction data which describes a correction of the initial segmentation for each patient of the first plurality of patients; acquiring atlas data which describes an image-based model of the anatomical body part; determining correction transformation data based on the segmentation correction data and the atlas data, wherein the correction transformation data describes a transformation for transforming the corrections into a reference system used for describing positions in the image-based model; determining transformed correction data based on the segmentation correction data and the correction transformation data by applying the transformation to the corrections to determine transformed corrections; determining combined correction data is determined based on the transformed correction data, wherein the combined correction data describes the results of a statistical analysis of the corrections; wherein a computer-implemented method of determining corrections for correcting the segmentation of medical image data further includes: acquiring segmented individual patient image data which describes a segmentation of the anatomical body part of the patient in a digital individual medical image; determining correction re-transformation data based on the atlas data and the individual patient image data, wherein the correction re-transformation data describes a transformation for transforming the results of the statistical analysis of the corrections into a reference system used for describing positions in the digital individual medical image; determining re-transformed correction data based on the combined correction data and the correction re-transformation data; and determining corrected segmented patient image data based on the individual patient image data and the re-transformed correction data, wherein the corrected segmented patient image data describes a result of applying the corrections to the segmentation of the anatomical body part of the patient in the digital individual medical image.
 15. A system, comprising: at least one computer having at least one processor and associated memory, the associated memory having instructions which when executed by the at least one processor causes the at least one processor to: determine distributions of corrections for correcting a segmentation of medical image data which includes: acquire initial segmented patient image data which describes an initial segmentation of digital medical images of an anatomical body part of a first plurality of patients; acquire segmentation correction data which describes a correction of the initial segmentation for each patient of the first plurality of patients; acquire atlas data which describes an image-based model of the anatomical body part; determine correction transformation data based on the segmentation correction data and the atlas data, wherein the correction transformation data describes a transformation for transforming the corrections into a reference system used for describing positions in the image-based model; determine transformed correction data based on the segmentation correction data and the correction transformation data by applying the transformation to the corrections to determine transformed corrections; determine combined correction data based on the transformed correction data, wherein the combined correction data describes the results of a statistical analysis of the corrections; wherein the instructions which when executed by the at least one processor causes the at least one processor to execute a computer-implemented method of determining corrections for correcting the segmentation of medical image data further includes: acquire segmented individual patient image data which describes a segmentation of the anatomical body part of the patient in a digital individual medical image; determine correction re-transformation data based on the atlas data and the individual patient image data, wherein the correction re-transformation data describes a transformation for transforming the results of the statistical analysis of the corrections into a reference system used for describing positions in the digital individual medical image; determine re-transformed correction data based on the combined correction data and the correction re-transformation data; determine corrected segmented patient image data based on the individual patient image data and the re-transformed correction data, wherein the corrected segmented patient image data describes a result of applying the corrections to the segmentation of the anatomical body part of the patient in the digital individual medical image; at least one electronic data storage device storing the initial segmented patient image data and the segmentation correction data; and wherein the at least one computer is operably coupled to the at least one electronic data storage device for acquiring, from the at least one electronic data storage device, the initial segmented patient image data and the segmentation correction data, and for storing, in the at least one electronic data storage device, at least the combined correction data and the corrected segmented patient image data.
 16. A system, comprising: at least one processor and associated memory, the associated memory having instructions which when executed by the at least one processor causes the at least one processor to: determine distributions of corrections for correcting a segmentation of medical image data which includes: acquire initial segmented patient image data which describes an initial segmentation of digital medical images of an anatomical body part of a first plurality of patients; acquire segmentation correction data which describes a correction of the initial segmentation for each patient of the first plurality of patients; acquire atlas data which describes an image-based model of the anatomical body part; determine correction transformation data based on the segmentation correction data and the atlas data, wherein the correction transformation data describes a transformation for transforming the corrections into a reference system used for describing positions in the image-based model; determine transformed correction data based on the segmentation correction data and the correction transformation data by applying the transformation to the corrections to determine transformed corrections; determine combined correction data based on the transformed correction data, wherein the combined correction data describes the results of a statistical analysis of the corrections; wherein the instructions which when executed by the at least one processor causes the at least one processor to execute a computer-implemented method of determining corrections for correcting the segmentation of medical image data which includes: acquire segmented individual patient image data which describes a segmentation of the anatomical body part of the patient in a digital individual medical image; determine correction re-transformation data based on the atlas data and the individual patient image data, wherein the correction re-transformation data describes a transformation for transforming the results of the statistical analysis of the corrections into a reference system used for describing positions in the digital individual medical image; determine re-transformed correction data based on the combined correction data and the correction re-transformation data; determine corrected segmented patient image data based on the individual patient image data and the re-transformed correction data, wherein the corrected segmented patient image data describes a result of applying the corrections to the segmentation of the anatomical body part of the patient in the digital individual medical image; at least one electronic data storage device storing the individual patient image data; wherein the at least one processor is operably coupled to the at least one electronic data storage device for acquiring, from the at least one electronic data storage device, the individual patient image data, and for storing, in the at least one electronic data storage device, at least the segmented individual patient image data; and data storage device for acquiring, from the data storage device, the data defining machine learning model parameters. 